Silica nanoparticles (SiNPs) are composed of silicon dioxide, the most abundant compound on Earth, and are used widely in many applications including the food industry, synthetic processes, medical diagnosis, and drug delivery due to their controllable particle size, large surface area, and great biocompatibility. Building on basic synthetic methods, convenient and economical strategies have been developed for the synthesis of SiNPs. Numerous studies have assessed the biomedical applications of SiNPs, including the surface and structural modification of SiNPs to target various cancers and diagnose diseases. However, studies on the in vitro and in vivo toxicity of SiNPs remain in the exploratory stage, and the toxicity mechanisms of SiNPs are poorly understood. This review covers recent studies on the biomedical applications of SiNPs, including their uses in drug delivery systems to diagnose and treat various diseases in the human body. SiNP toxicity is discussed in terms of the different systems of the human body and the individual organs in those systems. This comprehensive review includes both fundamental discoveries and exploratory progress in SiNP research that may lead to practical developments in the future.